Abstract 10085: Chronic Localized High-Frequency Electrical Stimulation Within the Myocardial Infarct Attenuates Infarct Expansion Through Transforming Growth Factor-β Signaling
Background: Structural events following myocardial infarction (MI) is the formation of a scar populated by metabolically active fibroblasts. These post-MI fibroblasts are responsive to signaling through the transforming growth factor-β (TGF) pathway, which includes activation of TGF receptors (TGF-R1 and TGF-R2) and transduction elements (SMAD-2/3). Accordingly, this study tested the hypothesis that localized high frequency stimulation (LHFS) instituted within a MI scar using low amplitude electrical pulses would prevent MI thinning through activation of the TGF signaling cascade in resident fibroblasts.
Methods: MI was surgically induced in pigs (n=17). At 3 wks post-MI, pigs were randomized for LHFS (n=7, 240 bpm, 0.8V, 0.05ms pulses at the center of the MI region) or unstimulated (UNSTIM, n=10). At 4 wks post-MI, LV volumes and wall thickness (echo) were measured. Levels of TGF, TGF-R1, TGF-R2, SMAD-2/3, phosphorylated SMAD-2/3 (pSMAD-2/3), and fibrillar collagen content (COLL, histology) in the remote and MI regions were determined and normalized to values in LV samples obtained from non-MI pigs (n=5, 100%).
Results: LV dilation between 3 to 4 weeks post-MI was lower with LHFS compared to UNSTIM (3.2±2.6% vs. 12.9±5.3%, respectively, p=0.03) with a concomitant thickening of the LV wall at the MI region (0.89±0.07 vs 0.67±0.08 cm, p<0.05). Within the MI region, levels of COLL, TGF, TGFR2, and pSMAD-2/3 were higher with LHFS than UNSTIM (TABLE).
Conclusions: These findings demonstrate that LHFS within the MI region attenuated LV dilation. Potential mechanisms include the regional activation of the TGF signaling cascade within resident fibroblasts. Thus, targeted electrical stimulation of the MI region can alter the endogenous substrate for post-MI remodeling. In light of the fact that multisite myocardial pacing is a commonly utilized clinical tool, then LHFS may provide a novel means to favorably modify LV remodeling post-MI.
- © 2010 by American Heart Association, Inc.